In chapter 6 of his letter to the believers in Ephesus, Paul commended them to make war properly with their enemies, by first knowing who the enemies were, and then knowing how to arm themselves with the mighty power of God Himself.
You know the armor parts – helmet, shield, breastplate & the rest. Verse 18, however, is also part of the instruction: “Pray in the Spirit…”
Paul used the phrase, “walk in the Spirit” several times in his letters. It makes sense: do what you do under the influence and leadership of the Holy Spirit. “Pray in the Spirit” means the same thing, only with regard to prayer, not walking.
The only influential Scripture that can help explain it is the similar phrase related to walking. Nothing in Ephesians 6 indicates anything different from that meaning. So, to impose on “pray in the Spirit” the idea that it means, “pray in tongues,” or “pray with your spirit” is inappropriate.
Paul wrote that we can speak, pray and sing with our spirit or with our understanding (1 Corinthians 14:15). I could be praying in English and be praying what the Spirit guides me to pray, and I am praying in the Spirit. I could be praying in tongues, not knowing what I am praying, but being led by the Spirit to pray what sounds come out of my spirit, and be praying in the Spirit. I could be praying with my mind or my spirit, in English or in tongues, and be so carnally minded that I am not at all praying in Him.