Liverpool-born Andrew Goodall has worked in the NHS for 23 years and is the ex-chief executive of Aneurin Bevan University Health Board.
He succeeds David Sissling, who was appointed chief executive of Kettering General Hospital NHS Foundation Trust earlier this year.
Dr Goodall said he was privileged to have been offered the post.
The Welsh government said Dr Goodall had worked in Wales for most of his life, having moved to the country at a young age.
He has a law degree from Essex University and a Ph.D in health service management from Cardiff Business School.
He became Aneurin Bevan University Health Board's chief executive in June 2009, and has led a number of national programmes and initiatives. Most recently he has supported a ministerial review into the handling of complaints which is due to report shortly.
He said: "I, of course, understand the pressures and expectations that the NHS faces, but also know that we have the responsibility and opportunity to make the necessary changes, including how we balance delivering our services with focusing on improving the long-term health of the Welsh population."
Dr Goodall will head the Welsh government's Department for Health and Social Services in addition to being chief executive of NHS Wales.

10 June 2016 Last updated at 08:36 BST
Chris Horn, from Newbury in Berkshire, came up with the idea whilst on his tractor and hopes the idea could spread across the UK.
He says the business model could help other young farmers but adds that 40% of their revenue goes on licensing fees.

The neighbours announced on Thursday that they had agreed to re-schedule peace talks which were postponed after the attack on an Indian air base.
Islamabad has arrested some members of the Jaish-e-Mohammad (JeM) group, which India blames for the attack.
Pakistani papers say the arrests saved the talks from breaking down.
The four-day assault on the Pathankot air force base in Punjab, close to the Pakistan border, started on 2 January, when a group of gunmen - wearing Indian army uniforms - entered residential quarters on the air base.
Some Pakistani papers urged Islamabad to take "tough decisions", adding that the arrests of some JeM members was "just the start".
The Express Tribune commended Pakistan's "constructive" response after the attack.
Echoing similar views, The Nation said the "efficiency" of the Pakistani government's investigation into the Pathankot attack was "unprecedented".
It added that India was still not ready to "trust" Pakistan despite the arrests of some JeM members, but this situation must "change" to establish lasting peace.
Pakistan Today wondered if Pakistan's "zero tolerance for terrorism will continue with the zeal being presently displayed".
Some papers argued that both India and Pakistan needed to work together to defeat terrorism.
The Daily Times remarked that militants were acting as "spoilers" in the India-Pakistan peace process.
It added that despite Islamabad's crackdown on JeM, it "had failed to dismantle the organisation which continues to operate openly in various districts".
Some Pakistan papers urged India to act "positively" after Pakistan's decision to investigate the Pathankot attack.
The News said the arrests of JeM members was an "important" step to improve Pakistan's ties with India. However, it added that it would be good to see some "cooperation" from India in "detecting outfits [groups] on its soil that operate within Pakistan".
Urdu daily Nawa-i-Waqt said India should react in a positive manner to the overtures made by Pakistan. It added that the onus was now on India to work towards the complete restoration of peace talks between the neighbours.
Another Urdu daily, Jang, argued that Pakistan had swiftly acted against the suspects of the Indian air base attack.
It added the move showed the "political and military establishment's pledge that the Pakistani soil won't be used for terrorism against India", and the neighbour must do the same.
A former health board chief has been appointed the new head of the NHS in Wales.
[NEXT_CONCEPT]
A fourth generation farmer has found a novel way to diversify his business by showing movies in his fields.
[NEXT_CONCEPT]
Pakistani papers have praised Islamabad for overcoming diplomatic tensions with India to continue peace talks efforts.