Wawrinka, seeded No. 3 and playing in his home country, was ousted by Paul-Henri Mathieu 7-6 (7-3), 7-6 (10-8). Each player dropped serve twice in the see-saw first set and held off a series of break points in the second to force the tiebreaker.
Thomaz Bellucci outlasted Youzhny, the No. 4 seed, for a 4-6, 6-2, 6-4 win that took more than 2 hours. Bellucci faced just one break point -- saving it -- in the final two sets.
Fifth-seeded Feliciano Lopez escaped the upset string by coming from behind for a 6-7 (3-7), 6-1, 6-4 win over Jan Hajek. Lopez won three-quarters of the points on serve and dropped 11 points total -- two on serve --- in turning the match around in the second set.
Ernests Gulbis also advanced to the quarterfinals, getting by Benoit Paire 5-7, 7-6 (7-3), 6-4. Gulbis fought off 15-of-17 break-point situations.
Also Wednesday, No. 7-seeded Santiago Giraldo beat Henri Laaksonen 6-2, 6-2 in a first-round match.
Swim Week Miami Beach 2014 [PHOTOS]