The Midland Main Line is a main railway line in the United Kingdom and is part of the British railway system.

The line links London (St Pancras) to Sheffield (Midland Station) in northern England, but also links other important population centres including Luton, Bedford, Wellingborough, Kettering, Market Harborough, Leicester (London Road), Loughborough, Long Eaton, Derby, Beeston, Nottingham and Chesterfield. The line is electrified between London and Bedford. And there are plans to build a station on the line to service East Midlands Airport.

Towards the London end the lines are also used for Thameslink services.

The Midland Main line was built between the 1830s and the 1860s largely by the Midland Railway company, the Leicester to London stretch of the line was built in the 1860s to relieve an earlier route to London via Rugby which had been built by the Midland Railway's predecessor the Midland Counties Railway and had become very congested.

The express services on the line are operated by a company called Midland Mainline.