Born in Farmington Hills, Michigan, DeBrincat spent one year at Harrison High School before transferring to Lake Forest Academy in Illinois.

There, he set a franchise record with over 50 goals and 100 points in his first season, and he won the Emms Family Award and CHL Rookie of the Year trophies.

During the 2016–17 season, DeBrincat became the all-time Otters goal leader and the top scorer of any OHL player born in the United States.

[5] Erie general manager Sherwood Bassin had scouted him during Lake Forest's 8–2 rout of the Soo Indians, in which DeBrincat scored three goals and recorded two assists.

[13] He added another nine goals and 16 points in 20 playoff games,[14] but the Otters lost to the Oshawa Generals in the J. Ross Robertson Cup finals.

[20] He was named the OHL Player of the Month after scoring 16 goals and 23 points in 12 games,[21] and he followed the award with his third hat-trick of the season, this time against the Peterborough Petes.

[32] DeBrincat and his teammate Taylor Raddysh were named the OHL's Co-Players of the Month for November 2016 after they both scored 27 points in 12 games.

[38] On February 21, DeBrincat joined Dale McCourt as the only two players in OHL history to score 50 goals in three consecutive seasons.

[40] In the final game of the regular season, a 5–2 win over the Guelph Storm, DeBrincat scored his 65th goal, a single-season record for the Otters.

[51] He earned preseason praise from head coach Joel Quenneville, who said DeBrincat "seems to have a good approach to the game" and "fit in well with his teammates" following a 4–2 victory over the Detroit Red Wings.

[52] DeBrincat ultimately made the opening night roster, making his NHL debut on October 4, 2017, and playing on the third offensive line with Patrick Sharp and Artem Anisimov.

[56] Promoted to the top line with Jonathan Toews and Anthony Duclair, DeBrincat broke a seven-game scoring drought on January 26 with his second hat-trick, this time against the Red Wings.

[69] On February 18, 2019, DeBrincat had a five-point game, adding two assists to his fourth career hat-trick in the Blackhawks' 8–7 win over the Ottawa Senators.

[73] He entered the 2019–20 season in a scoring drought, with only five goals through his first 23 games, but contributed as a playmaker, his 13 assists in that span second only to Patrick Kane's 18.

[74] DeBrincat snapped his 12-game goalless streak on December 5 when he scored on Tuukka Rask in the third period of the Blackhawks' 4–3 overtime win against the Boston Bruins.

[75] By the time that the COVID-19 pandemic forced the NHL to suspend operations in March 2020, DeBrincat had 18 goals, 27 assists and 45 points in 70 games, a significant decrease from the previous year.

[76][77] Shortly before the pandemic pause, Colliton told reporters, "He's had the chances, he's had as many opportunities this year, I think the puck hasn't gone in the net as often.

[83] DeBrincat and Kane were the Blackhawks' top offensive producers at the start of the COVID-shortened season, combining for 3.75 goals per game through the first third of the year.

[85] Outside of scoring, DeBrincat showed a significant increase in stealing the puck from opponents, a skill that he began practicing the season prior as a way to contribute during his goal droughts.

Entering the game on a seven-game scoreless drought, DeBrincat became the eighth player to record multiple 40-goal seasons as a member of the Blackhawks.

[100][101] On July 9, 2023, DeBrincat was traded to the Detroit Red Wings in exchange for Dominik Kubalík, prospect Donovan Sebrango, a conditional 2024 first-round draft pick and Detroit's 2024 fourth-round selection; the Red Wings then signed DeBrincat to a four-year contract extension with an average annual value of $7.875 million.

[102] DeBrincat, a Michigan-native, expressed enthusiasm in playing for Detroit, commenting "Growing up here and rooting for the Red Wings when I was younger, it's definitely a dream come true.

[105] Following the conclusion of his rookie NHL season, DeBrincat was one of four Blackhawks named to the United States senior team for the 2018 IIHF World Championship in Denmark.

[4] After four years at American International College, Andrew began playing professional ice hockey in 2019, and has appeared in the ECHL for the Cincinnati Cyclones and Kalamazoo Wings.