Reading your question, I assume you are using IIS for debugging, not Visual Studio Development Server.
In this case, debugging application start is tricky, because it is only called once when the application pool is started or recycled. When Visual Studio attaches to the process, Application_Start has already been running.
The trick is to make the application pool recycle without killing the process you are attached to.
Do the following:
- In Visual Studio (must be run as Administrator) set your breakpoint in
global.asax.cs and start debugging as usual (F5). The page opens in
your web browser, but the breakpoint isn’t hit. - Now the trick: With a text editor, open web.config from where it is
served by IIS, change it (e.g. enter a blank line somewhere) and
save it. In contrast to recycling the application pool in IIS, this
lets the application pool recycle (and thus running through
Application_Start in global.asax.cs the next time the web site is
called) without killing the process you are attached to. - In your web browser, reload the page. The breakpoint should be hit now!
That works for me (IIS 7.5, VS2015).