Southill station was opened by the Midland Railway in 1857 as part of its new line from Leicester to Hitchin via Bedford, enabling it to reach London King's Cross station by having running powers over Great Northern Railway metals from Hitchin southwards.

[3] The station was convenient for Southill Park, the seat of the Whitbread family who had supported and brought their influence to bear on the realisation of the line.

On 3 June 1890 a new signal box was opened at Southill as part of the introduction of block telegraph working between the station and the Midland Goods Yard at Hitchin.

Traffic picked up again during the Second World War when troop specials were run to enable conscripts to return home from the RAF camps at Cardington and Henlow.

Not far from the station in Southill Park is a stone obelisk erected in 1864 in honour of William Henry Whitbread whose influence and energy helped bring about the Bedford to Hitchin line.