Reigning champion Ivo Karlovic was knocked out of the first round of the Delray Beach Open after suffering a shock 6-3 3-6 6-2 loss against John-Patrick Smith on Monday.
Smith, the world number 135, took out the first set after winning an impressive 80 per cent of his first serve points.
Karlovic, who hit a total of 21 aces in the match, took out the second set but the 36-year-old's title defence suffered an abrupt ending as Smith rallied in the decider to complete an unlikely victory over the tournament's third seed.
The Australian will face the winner of one-time champion Juan Martin del Potro and Denis Kudla in the final 16.
Adrian Mannarino joins Smith in the next round thanks to a 1-6 6-3 6-1 win over Malek Jaziri.
Jaziri started strongly and dominated the eighth seed to take out the first set, but Mannarino showed his class to fight back into the match.
The Frenchman saved three breaks points in the second set before winning all three of his own break opportunities in the third to complete the victory.
Meanwhile, fourth-seed Grigor Dimitrov had no troubles against Dudi Sela, needing just over an hour in a 6-4 6-2 win over his Israeli opponent.