MLB Tonight is the signature program that airs on MLB Network and is simulcast on MLB Network Radio. The show offers complete coverage of all Major League Baseball games from 6 pm ET – 1 am ET during the regular season, and gives news from all 30 MLB teams during the offseason. It is taped live in Studio 3 of the MLB Network facility in Secaucus, New Jersey, but also features segments taped in Studio 42. The program aired from the beginning of Spring Training to the end of the World Series and was replaced in the offseason by Hot Stove, until it started to air in the offseason, and Hot Stove became MLB Network's weekday morning show. The show won the Sports Emmy Award for best Daily Outstanding Studio Show for 2010, 2011, 2012, 2014 and 2015.

MLB Tonight airs seven days per week, starting at 6 pm ET on weekdays until the last MLB game of the night has ended. MLB Tonight is followed by Quick Pitch, MLB Network's highlights show of record.

On Saturdays, the show airs before and/or after the Saturday Night Baseball game. In 2012, the Sunday edition of MLB Tonight was expanded to air from 1 pm to 8 pm ET.

On Deck Circle is a special 1-hour pre-game version of MLB Tonight airs leading up to the night's MLB Network Showcase. It is filmed from the same studios as MLB Tonight, however, will also include interviews from the stadium with the night's sideline host, and analytics from the night's play-by-play and analyst in the booth. It also includes the same highlights and analysis as MLB Tonight to fill time.