Highway 6 begins at the Canada–United States border. The border crossings are Raymond, Montana on Montana Highway 16 in the United States and at Regway, Saskatchewan on Highway 6.^[5] Two early name choices for Meyer were Meyersville or Fort Comfort the name of the neighboring North-West Mounted Police (NWMP) post to the north. Minton, became a hamlet in 1930 and in 1951 Minton incorporated as a village.^[6] The initial stages of the journey are mixed grassland, and the main economy is ranching.^[7] This area traversed is the Big Muddy Badlands area of the Missouri Coteau. The terrain of the Missouri Coteau features low hummocky, undulating, rolling hills, potholes, and grasslands. This physiographic region of Saskatchewan is the uplands Missouri Coteau, a part of the Great Plains Province or Alberta Plateau Region which extends across the south east corner of the province of Saskatchewan.^[8] There are several unique geographical features. The Big Muddy Valley, The Hole in the Wall Coulee, Roan Mare Coulee are all deep valleys of the area. The Big Muddy Lake, an alkali lake, could be crossed at the Diamond Crossing was a rise in Big Muddy Lake. Outlaw gangs such as the Jones-Nelson Gang used this undulating landscape to cross the border and hide out.^[9] Between the Canada customs port of Regway and Minton are several points of interest such as an old schoolhouse, and the historic Ceylon Park Memorial Garden.^[10] Gibson Creek is dammed with Ceylon Dam providing water to the village of Ceylon, as well as the Ceylon Regional Park which is located just off Highway 6.^[11] Besides passing ranches, oil and gas wells, agricultural lands producing feed, there are also Pregnant Mare Urine barns along this route.^[12] Highway 6 intersects the Red Coat Trail near Pangman at Ceylon.

Corinne is located at the Highway 6 and Highway 39 junction, where the two routes share a short concurrency. It is here that the northern journey of the CanAm Highway continues on Highway 6. The historic Wood Mountain - FortQu'Appelle Trail is marked with a point of interest marker.

The projects on Highways 39 and 6 will help to improve traffic flow through these Canada/U.S. ports. "Highways 6 and 39 are very important to Saskatchewan — serving as tourism links and major north-south trade corridors to the U.S.," Sonntag said.

Highway 6 reaches Regina, which is the capital of Saskatchewan and is the second largest in the province (after Saskatoon). Regina was previously the headquarters of the North-West Territories, of which today's provinces of Saskatchewan and Alberta originally formed part, and of the District of Assiniboia.^[15] The city is situated on a broad, flat, treeless plain. There is an abundance of parks and greenspaces: all of its trees — some 300,000^[16] — shrubs and other plants were hand-planted and Regina's considerable beauty is entirely man-made.^[17] As in other prairie cities, American elms were planted in front yards in residential neighbourhoods and on boulevards along major traffic arteries and are the dominant species in the urban forest. The IPSCO Wildlife Park is located off Highway 6 at Regina.^[18]

Highway 6 and Highway 1, the Trans-Canada Hwy, intersect at the Regina Bypass, located just south of Regina, at a partial cloverleaf interchange. The Regina Bypass is a $1.8 billion project that included 12 overpasses and 40 kilometres (25 mi) of four-lane highway, and opened in October 2019.^[19] As part of the project, the Highway 1 and Highway 11 designations were moved from Regina city streets to the Regina Bypass.^[20] Highway 6 continues north to a cloverleaf interchange at Ring Road (the former alignment of Highway 1) at the south end of Regina, it is one of the first two Saskatchewan interchanges which opened in 1967.^[14] Highway 6 is signed to follow Ring Road and bypass the downtown area;^[21][22] however, it officially follows Albert Street through the city.^[2] North of Victoria Avenue, Highway 6 shared a concurrency with Highway 11 (prior to the opening of the Regina Bypass) until the route reaches the north end of the Regina, where the routes rejoins Albert Street. Unsigned Highway 11A branches northwest towards Highway 11 and Saskatoon and Highway 6 leaves Regina.

The Qu'Appelle River flows east–west across the province, Highway 6 goes through the Qu'Appelle valley north of Regina. A crosswalk was installed at Southey, with overhead lights giving higher visibility to pedestrians crossing Highway 6 at Assiniboia Avenue.^[23]

In the Aspen Parkland ecoregion, deer and other large ungulates are a hazard to traffic, resulting in potential animal or human deaths, especially in the autumn mating months or when deer are searching for feeding grounds in the spring. The defence mechanism of deer in the face of a threat is to freeze. There are over 3,500 deer–auto collisions per year in Saskatchewan.^[24] A number of measures have been implemented to increase awareness such as fencing, feeding programs, automobile whistles.^[25] Deer mirrors along the edges of highways were installed for reducing deer-vehicle collisions.^[26] The Wildlife Warning System is triggered by highway vehicles, setting off lights, sounds and or odours ahead of the approaching vehicle to frighten away animals. A system that detects vehicle was installed in 2002 near Harris to reduce the quantity of mule deer–automobile accidents for a two-year testing period.^[27] Another system detects large animals and sets off a warning system to drivers of vehicles, alerting them that an animal is on or near the highway ahead of time.^[24][28]

McNab Regional Park is located south of Watson featuring pool and golf course.^[29] Watson is located amid the junction of Highway 5 and Highway 6.^[30] In this area Highway 6 is travelling through the boreal-transition ecoregion.

Highway 6 is a major north/south highway that has been experiencing higher volumes of truck traffic and general traffic, ... By strengthening the base of this section, we are ensuring Highway 6 will be able to support these heavier loads.

The highway travels east of Lake Charron upon which Lake Charron Regional Park offers camping, fishing, nature trails, and snowmobiling trails.^[32] Naicam is served by Highway 6, and Highway 349.^[33] This area is sustained by agriculture, with the ecosystem changing from the rolling parkland to boreal forest. The Barrier river valley, Kipabiskau Regional Park, and Lake Charron Regional Park are nearby features.^[34]

Highway No. 6 has a much higher traffic count, many more trucks in and out from the States than Highway No. 35 would have.

Melfort, a city of about 6,000, is located on Highway 6, Highway 3, and Highway 41.^[36][37] The CanAm Highway continues north on Highway 3.

The South Saskatchewan and North Saskatchewan Rivers join together west of the highway. The highway thus crosses the Saskatchewan River. The Fort à la Corne Provincial Park and the confluence of the Saskatchewan River Basin are two major attractions in this area.^[38] Choiceland is located 1 mile (1.6 km) north of Highway 55, the terminus junction of Highway 6.^[39] The Rural Municipality of Torch River No. 488 is located past the tree line of Saskatchewan. There are several recreational sites in the area such as Scot's Landing on the Saskatchewan River and Carrolls Cove Campground, Pruden's Point at Tobin Lake.^[40]

In 1999 the asphalt concrete pavement section of Highway 6 north of Raymore was tested with a Cold in-place recycling or “CIR” method to rehabilitate highways. This CIR process is a cost-effective method which recycles the top surface of a road. This pulverized material is mixed with asphalt emulsion and spread and compacted back onto the highway surface. This surface is then recovered with a new seal dependent on traffic volume.^[41]

From south to north:^[42]

Rural municipality	Location	km[1]	mi	Destinations	Notes
Surprise Valley No. 9	Regway	0.0	0.0	MT 16 south (Theodore Roosevelt Expressway) – Plentywood	Continuation into Montana
				Canada–United States border at Raymond–Regway Border Crossing
	​	6.7	4.2	Highway 18 west – Coronach	South end of Highway 18 concurrency
	​	16.4	10.2	Highway 18 east – Estevan	North end of Highway 18 concurrency
	Minton	18.6	11.6
The Gap No. 39	​	42.8	26.6	Highway 705 east – Colgate	South end of Highway 705 concurrency
	​	49.0	30.4	Highway 705 west – Bengough	North end of Highway 705 concurrency
	Ceylon	52.3	32.5	Highway 377 east – Radville
Norton No. 69	​	72.3	44.9	Highway 13 (Red Coat Trail) – Assiniboia, Weyburn	East of Pangman
Caledonia No. 99	​	93.6	58.2	Highway 712 west – Parry
	​	110.7	68.8	Highway 710 east – Milestone
	​	115.0	71.5	Highway 39 east / CanAm Highway – Weyburn	CanAm Highway south end; south end of Highway 39 concurrency
Bratt's Lake No. 129	Corinne	117.9	73.3	Highway 334 west – Avonlea
	​	118.7	73.8	Highway 39 west – Moose Jaw	North end of Highway 39 concurrency
	​	134.1	83.3	Highway 714 west – Rouleau
	​	140.6	87.4	Highway 306 east – Gray, Riceton
Sherwood No. 159	​	151.9	94.4	Highway 1 (TCH) (Regina Bypass) – Moose Jaw, Winnipeg	Interchange; Highway 1 exit 247
City of Regina		156.7	97.4	Ring Road to Highway 1 / Highway 6 north / Highway 11 north – Moose Jaw, Winnipeg, Airport	Interchange; Highway 6 north is signed to follow Ring Road but officially follows Albert Street (unsigned)[2]
		161.1	100.1	Albert Memorial Bridge crosses Wascana Creek
		162.3	100.8	Victoria Avenue to Highway 1 east
		166.7	103.6	Ring Road to Highway 1 / Highway 6 south – Airport	Interchange; Highway 6 south is signed to follow Ring Road but officially follows Albert Street (unsigned)[2]
		168.2	104.5	Highway 11A north (Louis Riel Trail) to Highway 11 – Lumsden, Saskatoon	Interchange; northbound exit and southbound entrance
Sherwood No. 159	No major junctions
Lumsden No. 189	​	176.2	109.5	Highway 734 – Lumsden, Zehner
	​	189.1	117.5	Highway 729 – Craven, Edenwold
	​	195.6	121.5	Highway 624 south – Zehner, Pilot Butte
Longlaketon No. 219	Fairy Hill	203.2	126.3	Highway 99 west – Craven
Cupar No. 218	Southey	219.7	136.5	Highway 22 – Earl Grey, Cupar, Fort Qu'Appelle
	​	234.3	145.6	Highway 731 west – Strasbourg
Touchwood No. 248	​	244.2	151.7	Highway 731 east – Ituna
Mount Hope No. 279	​	271.3	168.6	Highway 15 east – Ituna, Melville	South end of Highway 15 concurrency
	Raymore	273.9	170.2	Highway 15 west – Serath, Nokomis	North end of Highway 15 concurrency
	​	284.3	176.7	Highway 744 west – Nokomis
Big Quill No. 308	​	297.3	184.7	Highway 743 east – Wishart
	Dafoe	311.8	193.7	Highway 16 (TCH/YH) east – Yorkton	South end of Highway 16 concurrency
Prairie Rose No. 309	​	317.0	197.0	Highway 16 (TCH/YH) west – Lanigan, Saskatoon	North end of Highway 16 concurrency
Lakeside No. 338	​	339.8	211.1	Leroy access road
	Watson	354.9	220.5	Highway 5 east – Wadena	South end of Highway 5 concurrency
		355.2	220.7	Highway 5 west – Humboldt, Saskatoon	North end of Highway 5 concurrency
Spalding No. 368	​	376.4	233.9	Highway 756 west – Annaheim, Marysburg	South end of Highway 756 concurrency
	​	378.0	234.9	Highway 756 east – Rose Valley	North end of Highway 756 concurrency
Pleasantdale No. 398	Naicam	387.7	240.9	Highway 349 east – Archerwill Highway 777 west – Lake Lenore
	​	394.4	245.1	Lac Vert access road
	Pleasantdale	406.2	252.4	Highway 773 – St. Brieux, McKague
Star City No. 428	​	422.8	262.7	Highway 776 east – Resource	South end of Highway 776 concurrency
	​	431.5	268.1	Highway 776 west	North end of Highway 776 concurrency
City of Melfort		438.0	272.2	Highway 3 east – Tisdale Highway 41 west – Wakaw, Saskatoon	South end of Highway 3 concurrency
		441.2	274.1	Highway 3 west (Saskatchewan Avenue) / CanAm Highway / Broadway Avenue – Prince Albert	Highway 6 follows Broadway Avenue; CanAm Highway north end; north end of Highway 3 concurrency
Kinistino No. 459	​	458.6	285.0	Highway 778 west – Kinistino
Willow Creek No. 458	​	466.5	289.9	Fairy Glen access road
	​	473.1	294.0	Highway 789 west (Coxby Road)	South end of Highway 789 concurrency
	Gronlid	474.9	295.1	Highway 335 east – Arborfield
Nipawin No. 487	​	487.7	303.0	Highway 789 east – Codette	North end of Highway 789 concurrency
	​	490.5	304.8	Melfort Bridge across the Saskatchewan River
Torch River No. 488	​	508.4	315.9	Highway 790 east (Cherry Ridge Road)
	Choiceland	518.1	321.9	Highway 55 (NWWR) – Prince Albert, Nipawin Highway 692 north
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus       Incomplete access       Route transition

• Transportation in Saskatchewan
• Roads in Saskatchewan