The Strike Eagle has been deployed in Operation Desert Storm, Operation Allied Force, Operation Enduring Freedom, and Operation Odyssey Dawn carrying out deep strikes against high-value targets, combat air patrols, and providing close air support for coalition troops. It has also seen action in later conflicts and has been exported to several countries.

The F-15E will be upgraded with the Raytheon APG-82 Active Electronically Scanned Array (AESA) radar after 2007, and the first test radar was delivered to Boeing in 2010. It combines the processor of the APG-79 used on the F/A-18E/F Super Hornet with the antenna of the APG-63(V)3 AESA being fitted on the F-15C. The new radar upgrade is to be part of the F-15E Radar Modernization Program. The new radar was named APG-63(V)4 until it received the APG-82 designation in 2009. The RMP also includes a wideband radome (to allow the AESA to operate on more radar frequencies), and improvements to the environment control and electronic warfare systems.

While some of the F-15C/Ds have been replaced by the F-22 Raptor, there is no slated replacement for the F-15E in its primary "deep strike" mission profile. The Strike Eagle is a more recent variant of the F-15, and has a sturdier airframe rated for twice the lifetime of earlier variants. The F-15Es are expected to remain in service past 2025. The USAF has pursued the Next-Generation Bomber, a medium bomber concept which could take over the Strike Eagle's "deep strike" profile. The F-35A Lightning II is projected to eventually replace many other attack aircraft such as the F-16 Fighting Falcon and A-10 Thunderbolt II, and may also take over much of the F-15E's role; however, the F-15E has better combat range under payload.