Punch-Out!! is a 2009 boxing video game developed by Next Level Games and published by Nintendo for the Wii. It is the fifth and most recent mainline game in the Punch-Out!! series, following the SNES version of Super Punch-Out!!, and is a reboot of the series.

Following an early release at the Nintendo World Store in New York City on May 16, 2009, the game was released on May 18, 2009, in North America, May 22, 2009, in Europe, July 23, 2009, in Japan, and August 27, 2009, in Australia (exclusively at JB Hi-Fi stores). An additional WiiWare title, Doc Louis's Punch-Out!!, was released exclusively for North American Club Nintendo members on October 27, 2009. It was re-released under the Nintendo Selects label in 2011 for North American audiences only, as well as through the Wii U's Nintendo eShop in 2015 in all regions.

Upon release, Punch-Out!! received praise from critics for its gameplay, graphics, presentation, controls, and sense of nostalgia, though some criticism was given for its stereotypical character designs. It was also a commercial success for Nintendo, selling 1.27 million copies worldwide.

Punch-Out!! features a boxer named Little Mac working his way up the professional boxing circuits, facing a series of colorful, fictional boxers. The game requires reflexes to react to the computer-controlled boxers' moves. All of the boxers from the NES game except for Mike Tyson/Mr. Dream return, along with Bear Hugger and Aran Ryan from Super Punch-Out!! and new opponents Disco Kid, Giga Mac, and Donkey Kong. The game allows three different control schemes. The Wii Remote and Nunchuk can be used together, a Wii Balance Board can be used along with the Wii Remote and Nunchuk to duck or dodge, or the Wii Remote can be used by itself and held sideways in a traditional two-button control scheme.

In each stage, players must rely on quick reactions and identify various tells from their opponent to dodge or block their attacks, before returning with attacks to either the torso or the head with the left and right fists. Stars are awarded for landing a punch at particular moments, such as when an opponent grins or taunts Little Mac, and can be used to throw Star Punches that deal extra damage. The player can store up to three stars, but will lose them if hit by the opponent. Each fighter has a stamina gauge which results in a knockdown when fully depleted, with the player able to recover stamina while the opponent is down. Additionally, the player has a heart counter that decreases upon being hit, blocking an opponent's punch, or having a punch blocked by the opponent. If the counter reaches zero, the player will be unable to attack and will be vulnerable until they can successfully dodge an attack. A fight can end by knockout (KO), if a fighter is unable to rise within 10 seconds after being knocked down; by technical knockout (TKO), if a fighter is knocked down three times in one round; or by decision, if neither fighter achieves a KO or TKO after three rounds. Against certain opponents, the player can score an automatic KO by landing a Star Punch at the right moment, regardless of the opponent's stamina or number of knockdowns in the current round. The player also has a limited number of total knockdowns that can be sustained in a match. In Contender mode, the player has a maximum of four knockdowns. In Title Defense, that number is reduced to three. Once that number is exceeded, the player will be immediately knocked out with no chance to recover, even if they have not reached the three-knockdown threshold for a TKO. However upon reaching the maximum number of knockdowns, by mashing the A and B buttons during Little Mac's knockout animation, the player has a chance to save themselves through sheer will and return to the fight with a small fraction of health.

Two single-player campaign options are available. The Career option begins in Contender mode, in which Little Mac must climb the ranks of the World Video Boxing Association by rising through the Minor, Major, and World Circuits. Once Mac wins the world championship title, the game enters the more challenging Title Defense mode; he must now defend his belt against the other fighters, who use new techniques and defenses (such as King Hippo protecting his stomach with a manhole cover). Completing Title Defense unlocks Mac's Last Stand, an endurance mode in which Mac faces off against an endless series of randomly chosen opponents, one of whom is Donkey Kong. Once Mac loses three times, he retires from boxing and the Career option for the player's save file will become disabled, requiring the player to create a new file to play this option again. The Exhibition option allows players to fight against any opponents they have already defeated in either Contender or Title Defense, attempting to complete unique achievements, or practice against a holographic image of their current opponent. If the player wins 10 fights in Mac's Last Stand, an additional Champions Mode option is unlocked for Exhibition, in which a single hit will knock Mac down. Moreover, if during the Contender and Title Defense modes the player loses 100 fights, the headgear handicap will be unlocked, which significantly reduces the damage Little Mac takes from most attacks. However, this handicap is disabled in Mac's Last Stand.

New to the series is a split-screen multiplayer mode between Little Mac and a recolored clone. When one of the players has gathered enough power by repeatedly dodging all moves unscathed, that player's character transforms into a giant known as "Giga Mac" for a limited time and the game shifts to the opponent's single-player view until he returns to normal.

Doc Louis's Punch-Out!! is a standalone spin-off title and prequel, which was released on WiiWare as a Platinum reward for Club Nintendo members in North America on October 27, 2009. The game sees Little Mac sparring with his coach, Doc Louis, through three matches of increasing difficulty; the player wins each match by knocking Doc down once in three rounds. The game features three difficulty levels: Warm-up, Training, and Sparring. The game features the same graphics, voice acting, and game engine as the Wii version of Punch-Out!!, although it is not compatible with the Wii Balance Board.