Rooney moved to the brink of matching Bobby Charlton's England scoring milestone of 49 goals by clinching a 3-2 victory over Slovenia.
In Belarus, David Silva gave Spain a harder-than-expected 1-0 win to ensure Del Bosque could celebrate his 100th match in charge of the two-time defending champions.
Slovakia remained with England as the only sides to have won all six group qualifiers after seeing off Macedonia 2-1 to stay top of Group C, three points ahead of Spain.
Russia, meanwhile, slumped to a 1-0 home loss to Austria and has an uphill climb to earn automatic qualification for the 2016 finals in France as one of the top two teams in each group.
GROUP E
Rooney matched Gary Lineker's England haul of 48 goals as England kept its commanding lead of Group E.
Jack Wilshere finally bagged his first goals for England in his 28th international, scoring twice from outside the area. The two strikes in Ljubljana by the Arsenal midfielder wiped out Slovenia's 1-0 halftime lead, which Milivoje Novakovic had provided.
Although Nejc Pecnik produced an 84th-minute leveler, Rooney pounced two minutes later after collecting a pass from substitute Theo Walcott.
England completed the season unbeaten for the first time in 24 years — 12 months after the team exited the World Cup in the group stage with one point.
England has a six-point lead over Switzerland, which beat Lithuania 2-1, and a nine-point advantage over Slovenia.
The Swiss had to come from behind to win in Lithuania, with goals from Josip Drmic and Xherdan Shaqiri pushing them up to second.
Sergei Zenjov scored twice to lift Estonia to fourth place, two points behind Slovenia, with a 2-0 victory over San Marino.
GROUP C
Silva converted Spain's strong first-half performance into a goal just before the break, smashing in a cross from Cesc Fabregas that goalkeeper Andrei Gorbunov had misjudged.
However, Iker Casillas had to protect Spain's advantage with some timely saves in the second half.
It was Spain's 78th victory, to go with eight draws and 14 losses, since Del Bosque's debut in August 2008.
In Zilina, Kornel Salata started in place of injured defender Jan Durica and responded by heading in Slovakia's eighth-minute opener. Marek Hamsik made it 2-0 in the 38th before Arijan Ademi pulled one back for Macedonia in the 69th.
Ukraine beat Luxembourg 3-0 to stay in third place, three points adrift of Spain.
Belarus was left on four points, ahead of Macedonia with three and Luxembourg with one.
GROUP G
Marc Janko scored with a spectacular overhead kick as Austria maintained its grip on Group G with an away win over Russia.
Janko's winner came in the 33rd minute after Russia's Denis Glushakov has blocked two attempts by Zlatko Junozovic inside the penalty area. The rebound rose high and Janko timed his jump perfectly to score with his back to goal.
The result means Austria remains undefeated in the group with 16 points, eight clear of Russia, which is third.
Coach Fabio Capello's team has only won two of its last 10 competitive matches, including a win by default due to crowd trouble in Montenegro.
The Russians lost ground also to second-placed Sweden, which moved to 12 points by beating Montenegro 3-1 thanks to two goals by Zlatan Ibrahimovic.
At the bottom of the group table, Liechtenstein and Moldova drew 1-1 in Vaduz.
Del Bosque steps down as Spain coach after Euro 2016 exit
