The Chief Constable will take up the £208,000 role in the autumn after being selected by the Scottish Police Authority.
Mr House (54) has headed Strathclyde Police since 2007 and previously held senior roles with the Metropolitan Police.
He said: "I am delighted to accept this new and exciting post.
"My views on the creation of a single Police Service of Scotland have been widely publicised, so it gives me great professional pride to be trusted with the responsibility for developing and leading the new service.
"There are changes to make and these will not be easy.
"We need to organise ourselves better. We need to tackle inconsistencies in national systems and procedures while backing the local discretion of commanders to deal with local issues."
The new force will come into operation in April 2013.
Justice Secretary Kenny MacAskill said he was confident Glasgow-born Mr House would be an "outstanding" first chief constable of the single force.
"Stephen House has the skills and experience to lead the service as we embark on this new era," said Mr MacAskill.
"He has an impressive track record of leadership, partnership working and delivery."
Mr House will work alongside Vic Emery, who was recently chosen to head the new Scottish Police Authority.
The appointments come in the wake of a major shake-up of Scotland's police and fire services which will see the existing regional services merged into new nationwide organisations.
Mr Emery said Mr House would bring a wealth of experience to the role.
"Although we have both enjoyed long careers, we are both entering new and uncharted territory. That's challenging and exciting," he said.
"This is a historic moment in Scottish policing and together we have an opportunity to shape both the operational delivery of policing and the governance of policing to meet the complex challenges of the 21st century, and deliver improved outcomes for the people of Scotland.
"We recognise and welcome the huge responsibility we have been given."
Mr House spent the early part of his career at Sussex Police and has served with Northamptonshire, West Yorkshire and Staffordshire forces.
He was appointed deputy assistant commissioner at the Metropolitan Police in December 2001 and five years later took on the role of assistant commissioner with a responsibility for homicide, gun crime and fraud.
As chief constable of the Police Service of Scotland, he will earn a salary of £208,100 a year.
Mr MacAskill said: "Mr House will inherit a police service which is performing excellently - crime is at a 37- year low, assisted by over 1,000 additional officers we have delivered in communities since 2007, and public confidence is high.
"We are reforming from a position of strength - and Vic Emery and Stephen House will work together to ensure a smooth transition into a new Police Service of Scotland we can be proud of."