Substitute Jabo Ibehre earned Cambridge their first win of the season as Crawley continued their losing start to the season with a 1-0 home defeat.
Ibehre broke the deadlock on 63 minutes when a shot from Uche Ikpeaku was parried by goalkeeper Glenn Morris and the striker tucked in the rebound from close range.
Crawley went close early on when midfielder Mark Randall rattled the crossbar with a dipping long-range effort while at the other end, Ikpeaku was foiled by a smart Morris save.
Enzio Boldewijn failed to connect with a cross from Jordan Roberts for the hosts before Ikpeaku had a shot on the turn tipped over the bar by the alert Morris.
Crawley began the second half in lively fashion and Randall had a goal-bound shot blocked from the edge of the area but they fell behind through Ibehre's composed finish.
Dutch striker Thomas Verheydt and Matt Harrold both came close to equalising for Harry Kewell's side, who are rooted to foot of the League Two table.