Embiid was dominant in every facet, with his 59 points coming on 19-of-28 shooting, making 20-of-24 from the stripe, while having 11 rebounds, eight assists and seven blocks.
The Sixers center is the first player since blocks became official in 1973-74, to record 50-plus points, 10-plus rebounds, five-plus assists and five-plus blocks in a game.
Embiid is also the first player since Damian Lillard in 2019 to have more than half of his team's points in a game.
The Cameroonian erupted in the fourth quarter with 26 points, taking him into fifth spot for the best scoring performances in franchise history. It was a career-best points haul for 28-year-old Embiid.
Garland briefly holds season-high points haul
Garland's 51 points, which included 10 triples, was briefly a league season-high, before Embiid's monster game for the Sixers.
The Timberwolves led by 24 points late in the third before the Cavs rallied, led by Garland, who became the fourth Cleveland player to reach 50 points.
Karl-Anthony Towns scored 29 points with 13 rebounds, while D'Angelo Russell added 30 points with 12 assists.
AD lifts Lakers without LeBron to snap skid
Anthony Davis stepped up in LeBron James' absence, scoring 37 points with 18 rebounds as the Los Angeles Lakers snapped their five-game losing run with a 116-103 win over the Brooklyn Nets.
Davis shot 15-of-25 from the field, while bringing down 10 offensive rebounds among his 18 for the game, with Lonnie Walker adding 25 points, making four-of-five from beyond the arc.