Ramon Sessions had 16 points, Khris Middleton and Brandon Knight scored 15 each, and Giannis Antetokounmpo posted 13 for the Bucks (11-45), who own the NBA's worst record. John Henson chipped in 12 points for the Bucks, who had their highest scoring game of the season.
Philadelphia (15-42), which owns the league's second worst record, has lost 21 of 24 and 10 straight at home. It is the club's longest skid since a 12-game losing streak during the 1996-97 season.
Thaddeus Young led the 76ers with 28 points, Michael Carter-Williams added 20, Tony Wroten had 19, and James Anderson scored 13.
The Bucks had lost two in a row, 21 of 24, and 10 straight on the road. Their last away victory was against the Los Angeles Lakers on Dec. 31, 2013.
Milwaukee still hasn't won back-to-back games this season. Only 12,216 were in attendance for this one.
Philadelphia trailed 73-44 at halftime, the most points the 76ers had allowed in any half this season. It got worse as the Bucks' lead swelled to 33 points in the third quarter.
Mayo made his first five 3-point attempts. His sixth turned into a four-point play with 3.9 seconds remaining in the third quarter, giving the Bucks a 106-76 advantage.
The Sixers had 11 available players, including guard Eric Maynor and centers Henry Sims and Byron Mullens.
But the biggest name from their four deals before the NBA trade deadline on Thursday was inactive. Forward Danny Granger, a former All-Star who was acquired from the Indiana Pacers for forward Evan Turner and forward-center Lavoy Allen, was in town but not at the arena.
Sixers coach Brett Brown said before the game that a decision on Granger's status could be made within the next day.
NOTES: Bucks F Caron Butler sat out with a sprained left ankle. . The Sixers managed only 13 rebounds in the first half. . The Bucks' 73 points in the first half were a season-high in any half. . Bucks F Jeff Adrien had 10 rebounds.