Stephen Hunt scored Reading's winner just before halftime and Everton, who had won their opening two matches to top the table, could find no way back after the break.
Tottenham got back on track after a poor start to the season with two goals from Steed Malbranque and one from Jermaine Jenas killing off a poor Derby side inside the opening 15 minutes.
Wigan Athletic joined Everton on six points with a 3-0 defeat of Roy Keane's Sunderland while Portsmouth's impressive start continued with a 3-1 defeat of Bolton Wanderers who are still searching for their first point.
Middlesbrough and West Ham United secured their first victories of the campaign, winning away at Fulham and Birmingham City respectively.
Champions Manchester United play Manchester City on Sunday when Chelsea also travel to Liverpool.